Description using mathematical model has been attempted regarding substance concentration in biological body, in particular, blood glucose level and blood insulin concentration for medical reasons as represented by diagnosis of diabetes. The model used herein includes Bergman's minimal model (e.g., Bergman et al., American Journal of Physiology, vol. 236(6), p. E-667-77 (1979), and Bergman et al., Journal of Clinical Investigation, vol. 68(6), p. 1456-67 (1981)).
The minimal model uses blood glucose level, blood plasma insulin concentration, and insulin acting amount at the peripheral tissue insulin acting point, that is, remote insulin as variables. Assuming the blood glucose level at time t is G(t), blood plasma insulin concentration is I(t), and remote insulin is X(t), G(t), I(t), and X(t) are expressed by the following differential equations having the temporal differentiation on the left hand side.dG(t)/dt=−p1(G(t)−Gb)−X(t)G(t)dX(t)/dt=−p2X(t)+p3(I(t)−Ib)dI(t)/dt=−n(I(t)−Ib)+γ(G(t)−h), (where, G(t)>h)=−n(I(t)−Ib)+γ(G(t)−h), (where G(t)<=h)
Each parameter in the equation is,
p1: insulin non-dependent glucose metabolic rate
Gb: blood glucose level base value
p2: insulin intake function at insulin action point
p3: insulin consumption rate with respect to insulin dependent glucose metabolism
Ib: insulin concentration base value
n: insulin consumption per unit time
γ: insulin secretion sensitivity with respect to glucose stimulation
h : threshold value of blood glucose level when insulin secretion starts
The values differ among individuals.
Basically, four blocks of pancreas for secreting the insulin according to stimulation of blood glucose level, liver for taking up glucose from the blood or discharging glucose to blood according to the insulin concentration and the blood glucose level, circulation dynamic system for distributing insulin to peripheral tissues, and peripheral tissues for metabolizing glucose in response to the action of insulin associate with each other in the biological body to control the blood glucose level. In the minimal model, the components of the model are abstract elements that do not correspond to the four blocks of the biological body, and thus it is difficult to consider the simulation result of the change in blood glucose level and the change in insulin concentration of the biological body in association with the four blocks of the biological body.
Another blood glucose level reproducing method includes a method of predicting the blood glucose level in a diabetic patient (see e.g., U.S. Pat. No. 5,971,922). The blood glucose level may be predicted with such method, but the state of the organs related to blood glucose control is not known.
Therefore, Sysmex Corporation proposed a simulation system for obtaining the state (clinical condition) of the function of the liver such as the saccharometabolism in the liver which is effective in treating diabetes (U.S. Patent Application Publication No. 2006/0277015).
This simulation system for simulating a function of a biological organ, comprises:
a biological model in which the functions of the biological organs are expressed by mathematical models,
wherein the biological model comprises a hepatic metabolism model block having specified input and output relating to hepatic function for simulating the hepatic function, and
wherein the system further comprises arithmetic means for calculating an output value by using measurable status variables of a liver based on input value to the hepatic metabolism model block.
In such simulation system, the liver block that simulates the function of the liver outputs an output value using an actually measurable state variable, and the parameters in the mathematical model representing the function of the liver are optimized by comparing the result of simulation and the actually measured state variable. As a result, a model that represent the function of the liver more approximately is obtained, and the liver function related to liver disease is accurately simulated.